Mouse Model Study Supports Sexual Transmission of Zikavirus Infection

A newly established mouse model, which is expected to accelerate efforts to develop a vaccine to protect against Zikavirus (ZIKV) infection, revealed high levels of the virus in the testes of the animals, a finding that supports the possible sexual transmission of the disease.

Investigators at Washington University School of Medicine (St. Louis, MO, USA) used wild-type (WT) C57BL/6 mice, as well as a large panel of immune-deficient transgenic mice together with several different strains of ZIKV including a contemporary clinical isolate. In this study, the mice were infected via the skin in a manner that mimicked the bite of the mosquito vector of the disease.

The investigators reported in the April 5, 2016, online edition of the journal Cell Host & Microbe that whereas four- to six-week-old WT mice did not develop clinically apparent disease, mice lacking interferon alpha/beta (IFN-alpha/beta) signaling (genetically engineered triple knockout [TKO] mice) succumbed to infection with all the different ZIKV strains. Viral burden analysis revealed that mice lacking the interferon receptor (Ifnar1−/− mutants), but not WT mice, sustained high levels of ZIKV in all tissues tested, including serum, spleen, brain, spinal cord, and testes. The testes of Ifnar1−/− mice had the highest viral loads, which is relevant to the possible sexual transmission of ZIKV.

"Now that we know the mice can be vulnerable to Zika infection, we can use the animals to test vaccines and therapeutics - and some of those studies are already underway - as well as to understand the pathogenesis of the virus," said senior author Dr. Michael Diamond, professor of medicine at Washington University School of Medicine.

"We looked for evidence of Zika in the mouse testes mostly as an afterthought, due to mounting evidence of sexual transmission and were surprised that viral levels were the highest we saw in any tissue," said Dr. Diamond. "We are now doing subsequent tests to determine how long those viral levels are sustained, which could help us estimate the length of time Zika can be transmitted sexually."

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